Chapter 8 - Week 4

Psychosis & Schizophrenia Overview

• Psychosis: An inability to tell the difference between what is real and what is unreal.

• Schizophrenia: A severe psychiatric disorder where the core characteristic is that contact with reality is disrupted.

• Most people develop psychotic disorders in their late teens or early adult years.

Five Domains of Symptoms in Psychotic Disorders

Four positive symptoms:

1. Delusions.

2. Hallucinations.

3. Disorganized thought (speech).

4. Disorganized or abnormal motor behavior (including catatonia).

• Negative symptoms: Restriced emotional expression or avolition/affect.

  • Note: Cognitive deficits are very common, but they are not an official diagnostic criterion.

Types of Delusions (List of 8 Themes)

Delusions are irrational beliefs that are maintained despite being contradicted by reality or rational argument:

• Persecutory delusions: Believing one is being watched, tormented, or spied on by people they know or by authorities (e.g., FBI).

• Delusion of reference: Believing that random outside events, comments, or news broadcasts are directed specifically at them (e.g., weather forecast messages).

• Grandiose delusions / Megalomania: Believing that one is a special being, supreme ruler, or holds exceptional power and wealth.

• Delusion of thought insertion: Believing outside forces or people are putting thoughts directly into one's mind.

• Thought broadcasting: Believing that one's private thoughts are being broadcast loudly for others to hear.

• Thought withdrawal: Believing that thoughts are being stolen or removed from one's mind by an external force.

• Delusions of guilt or sin: Believing one is personally responsible for an awful disaster or catastrophe.

• Somatic delusions: Believing that part of one's body is diseased, rotting, dead, or altered in an impossible way.

Hallucinations: Types & Sensory Modalities

Unreal perceptual experiences occurring without an actual external physical stimulus.

• Auditory hallucinations: The most common form (hearing voices running a commentary on behavior, issuing commands, or arguing).

• Visual hallucinations: Often paired with auditory ones and consistent with delusions.

• Tactile hallucinations: Feeling sensations on the outside of the body (e.g., bugs crawling on skin).

• Somatic hallucinations: Feeling internal physical sensations inside the body (e.g., worms eating intestines or a burning sensation inside organs).

Hallucinations happen in all kind of disorders.

Formal Thought Disorder (Disorganized Thought and Speech)

Disorganized thinking manifested through broken speech patterns:

• Loose associations / Derailment: Slipping from one topic to a completely unrelated topic with little to no logical transition.

• Word salad: Speech so severely disorganized that words are thrown together incoherently.

• Neologisms: Making up completely new words that have meaning only to the patient.

• Clangs: Making associations based purely on the sounds/rhymes of words rather than their meaning.

• Sex difference: Men show more severe language deficits than women because women show bilateral language processing (both hemispheres), providing a neurological buffer.

Disorganized & Catatonic Behavior

• Disorganized behavior: Unpredictable agitation, pacing, inappropriate public acts (e.g., shouting, disrobing), and failing to complete basic tasks like dressing or eating because of hallucinations or delusions.

• Catatonia: Disorganized motor behavior reflecting complete unresponsiveness to the environment:

  • Negativism: Lack of response to instructions.

  • Catatonic posturing: Rigid, bizarre posture held against gravity for hours.

  • Mutism: Complete absence of speech and motor responsiveness.

  • Catatonic excitement: Purposeless, excessive motor agitation with no clear cause.

Negative Symptoms of Schizophrenia (Loss of Function)

Involve the loss or absence of normal psychological qualities; more persistent and less responsive to typical antipsychotic medications compared to positive symptoms:

1. Restricted affect: Severe reduction or absence of emotional expression, flat voice tone, lacking gestures, and blank facial expressions.

2. Anhedonia: Loss of the ability to experience pleasure.

3. Avolition / Apathy: Inability to initiate or persist in goal-directed activities at work, school, or home (poor hygiene, grooming, and lack of motivation).

4. Asociality: Extreme social withdrawal and total lack of interest in social interactions or relationships with family or friends.

Cognitive Deficits in Schizophrenia

• Deficits in attention, working memory, and processing speed.

• Patients struggle to maintain focus on relevant information and cannot suppress irrelevant background noise.

• Often emerge early (before the first acute psychotic break) and typically do not improve throughout the course of the disorder or with treatment.

DSM-5 Diagnostic Criteria for Schizophrenia (The 3 Core Symptoms Rule)

• Must show ≥2 symptoms of psychosis for at least 1 month.

• Mandatory Rule: At least one of the symptoms MUST be one of the top three:

  1. Delusions

  2. Hallucinations

  3. Disorganized speech

• Continuous signs of disturbance must persist for at least 6 months (including prodromal or residual phases) and cause functional impairment.

Prodromal vs. Acute vs. Residual Phases Schizophrenia

• Prodromal phase: The period before the first acute break; gradual withdrawal, eccentric behavior, and mild/subthreshold psychotic symptoms.

• Acute phase: Active symptoms present for at least 1 month (hallucinations, delusions, severe disorganization).

• Residual phase: Occurs after the acute break; positive symptoms subside, but negative symptoms and cognitive blunting remain.

Prognosis and Mortality in Schizophrenia

• Life expectancy is 10 to 20 years shorter than the general population due to medical comorbidities (cardiovascular disease, diabetes, cancer) and high suicide rates.

• Suicide rate: 5% to 10% die by suicide.

• Over the lifespan, positive symptoms tend to become less severe as dopamine activity declines with age, but negative symptoms often persist or worsen.

• Only about 20% experience an optimal recovery or clear remission.

Gender Differences & The Estrogen Protection Hypothesis

• Women have a more favorable overall prognosis than men: fewer hospitalizations, shorter inpatient stays, and milder negative symptoms.

• Estrogen Protection: Estrogen acts as a protective neurobiological buffer in females, dampening dopamine hyper-reactivity and delaying the onset of acute psychosis until later in life.

Sociocultural Factors: Developing vs. Developed Countries

Schizophrenia follows a more mild course in developing countries compared to developed nations.

• Why? Developing nations provide broader, closer family networks where care is shared; families score lower on hostility, criticism, and overinvolvement (lower expressed emotion), leading to lower relapse rates.

Schizoaffective Disorder

• A mixture of schizophrenia symptoms and a major mood disorder (major depressive or manic episode) occurring simultaneously.

• Psychotic symptoms (delusions or hallucinations) must be present for at least 2 weeks in the absence of a prominent mood episode during the lifetime course of the illness.

Differential Diagnosis by Duration (Exam Mnemonic!)

• 1 day to less than 1 month: Brief Psychotic Disorder (sudden onset of delusions, hallucinations, or disorganized speech that fully remits).

• 1 month to less than 6 months: Schizophreniform Disorder (meets full psychotic criteria for schizophrenia, but has not reached the 6-month threshold).

• More than 6 months: Schizophrenia.

Delusional Disorder vs. Schizotypal Personality Disorder

• Delusional Disorder: Presence of non-bizarre or bizarre delusions lasting at least 1 month without any other psychotic symptoms (no hallucinations, no thought disorder) and without daily functioning being severely impaired.

• Schizotypal Personality Disorder: A lifelong, pervasive pattern of eccentric behavior, magical thinking, odd speech, and social anxiety that does not cross the line into full psychotic episodes.

Four Major Biological Theories of Schizophrenia

• Genetic transmission: High heritability across families, twins, and adoptees.

• Structural and functional brain abnormalities: Reductions in gray matter, enlarged ventricles, and prefrontal deficits.

• Birth complications and prenatal exposure: Birth hypoxia, prenatal viral infections, and early neurological insults.

• Neurotransmitter theories: Excess dopamine activity, along with imbalances in serotonin, GABA, and glutamate.

Genetic Studies in Schizophrenia (Family, Adoption, and Twin Evidence)

• Family studies: The risk of developing schizophrenia decreases as genetic similarity to an affected individual decreases.

• Adoption studies: Biological relatives of adoptees with schizophrenia are 10 times more likely to have schizophrenia than biological relatives of healthy adoptees; adoptive relatives show no increased risk.

• Epigenetics: Environmental stressors alter whether genes are turned on or off without altering DNA sequence, affecting dopamine regulation and brain development.

Structural Brain Abnormalities: Gray Matter, Prefrontal Cortex & Hippocampus

• Gross reduction in gray matter: Especially in medial, temporal, superior temporal, and prefrontal areas.

• Prefrontal cortex (PFC): Undergoes major development from adolescence to young adulthood; people with schizophrenia show abnormal activation and structural deterioration here, impairing language, emotional expression, and planning.

• Hippocampus: Shows abnormal volume, shape, and activation, impairing the formation of long-term memories.

• White matter reductions: Impairs the ability of different brain regions to communicate.

Enlarged Ventricles in Schizophrenia

• Fluid-filled spaces in the brain that are visibly enlarged in people with schizophrenia.

• Signifies atrophy or deterioration of surrounding brain tissue.

• Patients with enlarged ventricles show social, emotional, and behavioral deficits long before developing overt positive psychotic symptoms, and they respond more poorly to typical medications.

Birth Complications & Perinatal Hypoxia

• Serious perinatal difficulties occur more frequently in the histories of people with schizophrenia than healthy controls.

• Perinatal hypoxia: Oxygen deprivation at birth or in the few weeks before/after birth.

• Mechanism: Hypoxia interacts with genetic vulnerability, directly damaging early neurological development and triggering later schizophrenia.

Prenatal Viral Exposure & The 2nd Trimester Vulnerability Window

• High rates of schizophrenia occur in offspring of mothers exposed to viral infections (pathogenic insults) while pregnant.

• Critical window (2nd trimester): Fetal neuro-blast cell migration to the cerebral cortex peaks during the second trimester. Disruptions during this window permanently alter cortical cytoarchitecture.

Gut Microbiome and Schizophrenia

• The gut microbiome (bacteria, fungi, and viruses in the gastrointestinal tract) communicates along the gut-brain axis.

• Disruptions in the microbiome significantly impact brain function and inflammation, and have been linked to an increased risk of psychiatric illnesses, including schizophrenia.

The Original vs. Revised Dopamine Theory of Schizophrenia

• Original theory: Schizophrenia is caused by simple excess levels of dopamine throughout the whole brain. Supported by phenothiazines/neuroleptics (which block dopamine and reduce symptoms) and amphetamines (which increase dopamine and induce psychosis).

• Revised (Dual-Path) model: Symptoms result from different levels of dopamine in distinct brain regions rather than a uniform excess.

The Dopamine Dual-Path Model (Mnemonic!)

• Mesolimbic pathway: Dopamine EXCESS (overschot) → causes Positive Symptoms (delusions, hallucinations, thought disorder) by attributing abnormal salience to otherwise harmless stimuli.

• Prefrontal cortex: Dopamine DEFICIT (tekort) → causes Negative Symptoms and cognitive deficits (avolition, flat affect, blunted motivation).

Social Drift vs. Urban Birth Hypothesis

• Social drift: Schizophrenia symptoms interfere with education and employment, causing affected individuals to downwardly drift into lower socioeconomic classes and unsupportive urban environments compared to their families of origin.

• Urban birth / Sociogenic hypothesis: Being born and raised in a crowded large city increases schizophrenia risk due to overcrowding, higher exposure to infectious agents, poverty, discrimination, and bullying.

Stress, Trauma, and Relapse in Schizophrenia

• High life stress frequently precedes an acute psychotic episode or relapse.

• Childhood adversity (emotional neglect, physical abuse, parental death) increases the likelihood of developing psychosis.

• Protective factor: Exposure to household pets (especially dogs) during infancy is linked to altered cortisol release, fewer immune disorders, and a lower risk of developing psychosis.

Expressed Emotion (EE) in Families (Exam Alert!)

A family interaction style marked by:

1. High hostility toward the patient.

2. Frequent, severe criticism.

3. Emotional over-involvement / overprotectiveness.

Core Rule: High Family Expressed Emotion is one of the strongest environmental triggers for psychotic relapse. Sufferers in high-EE homes relapse significantly faster than those in low-EE homes.

Cognitive Perspectives on Schizophrenia

• Deficits in attention and sensory gating cause an overwhelming flood of sensory input.

• To make sense of this confusing input, patients adopt cognitive thinking biases (e.g., jumping to conclusions, attributing external agency), which crystallize into delusions and hallucinations.

• Negative symptoms develop as an active coping strategy: patients isolate and limit activities to protect their depleted cognitive resources.

Typical (First-Generation) Antipsychotics: Chlorpromazine & Mechanism

• Include phenothiazines (e.g., chlorpromazine) and butyrophenones.

• Mechanism: Act as dopamine receptor antagonists (block D2 receptors), reducing agitation, delusions, and hallucinations.

• Limitation: Highly effective for positive symptoms, but have little effect on (and can sometimes worsen) negative symptoms. Around 25% of patients do not respond.

Side Effects of Typical Antipsychotics: Akathesia & Tardive Dyskinesia

• Common side effects: Sedation, dry mouth, blurred vision, sexual dysfunction, weight gain, constipation, menstrual irregularities, and akathesia (agitated inability to stay still).

• Tardive Dyskinesia (TD): A severe neurological disorder involving involuntary, repetitive movements of the tongue, face, mouth, or jaw (lip smacking, tongue protrusion).

• Exam Tip: Tardive Dyskinesia is often irreversible! Lowering the dosage or switching immediately to an atypical antipsychotic is required at the earliest sign of facial tics.

Atypical (Second-Generation) Antipsychotics & Agranulocytosis

• Include clozapine, risperidone, olanzapine, quetiapine, and ziprasidone.

• Mechanism: Bind to D4 dopamine receptors and also influence serotonin, relieving positive symptoms while treating negative symptoms better than typical drugs.

• Do not produce severe motor neurological symptoms (lower TD risk).

• Clozapine risk (Agranulocytosis): A dangerous deficiency of granulocytes (white blood cells) produced by bone marrow that impairs fighting infections; requires mandatory regular blood testing.

• Other side effects: Extreme weight gain, sedation, elevated diabetes risk, cardiac complications, and low blood pressure.

Cognitive-Behavioral Therapy (CBT) for Schizophrenia

• Teaches clients to challenge demoralizing attitudes about having schizophrenia.

• Teaches patients to test and dispute delusional beliefs or auditory hallucinations using behavioral experiments.

• Example: A patient hearing commanding voices conducts an experiment by ignoring the voice's command to verify that doing so does not result in catastrophe.

Family Therapy for Schizophrenia

• Combines psychoeducation about schizophrenia with behavioral training for family members.

• Aims to reduce High Expressed Emotion (EE) by increasing family tolerance for uncontrollable symptoms and teaching effective communication and conflict resolution.

• Improves medication adherence and significantly lowers psychotic relapse rates compared to drug therapy alone.

Assertive Community Treatment (ACT) Programs

• The gold-standard community-based system providing comprehensive 24/7 care.

• Utilizes an interdisciplinary team (medical professionals, social workers, psychologists) delivering services directly to patients in their natural environments/homes.

• Provides life skills training, vocational rehabilitation, crisis intervention, and medication management to decrease psychiatric hospitalizations.

Four Models of Cross-Cultural Traditional Healers

In non-Western societies, symptoms of schizophrenia are often managed by folk or religious healers through four distinct models:

1. Structural model: Reintegrating physical, emotional, and social balance.

2. Social support model: Surrounding the patient with extended community support.

3. Persuasive model: Shifting cognitive meanings through rituals and spiritual authority.

4. Clinical model: Direct physical herbal or somatic interventions.

In many developing countries, care for people with schizophrenia is more likely to be carries out by family than mental health institution.

Stigma and Schizophrenia: Biological vs. Psychosocial Attribution

• Stigma leads to negative stereotypes, fear, avoidance, discrimination, and avoidance of mental health treatment.

• Paradoxical finding: Attributing mental illness purely to biological causes (rather than psychosocial causes) leads members of the public to demand greater social distance from individuals with schizophrenia, worsening interpersonal isolation.